Niemann–Pick Type C Mutations Cause Lipid Traffic Jam

• Published in: Traffic (Copenhagen, Denmark) Vol. 1; no. 3; pp. 218 - 225
• Main Author: Liscum, Laura
• Format: Journal Article
• Language: English
• Published: Copenhagen Blackwell Publishing Ltd 01.03.2000
• Subjects: Animals; Biological Transport - genetics; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - physiology; CHO Cells - metabolism; cholesterol; Cholesterol - metabolism; Cholesterol, LDL - metabolism; Cricetinae; Cricetulus; Endoplasmic Reticulum - metabolism; Endosomes - metabolism; Fibroblasts - metabolism; Glycoproteins - chemistry; Glycoproteins - genetics; Glycoproteins - physiology; Humans; Intracellular Membranes - metabolism; late endosome; lipid transport; lysobisphosphatidic acid; lysosome; Lysosomes - metabolism; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - genetics; Membrane Glycoproteins - physiology; Membrane Lipids - metabolism; Models, Biological; Models, Molecular; multivesicular body; Niemann-Pick Diseases - genetics; Niemann-Pick Diseases - metabolism; Niemann–Pick C; Protein Conformation; Protein Structure, Tertiary; sphingolipid; Sphingolipids - metabolism; Transport Vesicles - metabolism
• ISSN: 1398-9219; 1600-0854
• DOI: 10.1034/j.1600-0854.2000.010304.x

The Niemann–Pick C protein (NPC1) is required for cholesterol transport from late endosomes and lysosomes to other cellular membranes. Mutations in NPC1 cause lysosomal lipid storage and progressive neurological degeneration. Cloning of the NPC1 gene has given us tools with which to investigate the function of this putative cholesterol transporter. Here, we discuss recent studies indicating that NPC1 is not a cholesterol‐specific transport molecule. Instead, NPC1 appears to be required for the vesicular shuttling of both lipids and fluid‐phase constituents from multivesicular late endosomes to destinations such as the trans‐Golgi network.